Studies completed have documented the natural history, as well as the altered behavioral and associated electrophysiological thresholds, of the chronic stimulant intoxication syndrome. The syndrome develops in at least three phases: 1) initial; 2) ontological development of end-stage behaviors; and 3) long-term residua. Each stage responds differentially to manipulation. The end-stage and residual syndromes are multidetermined; the hypothetical interacting mechanisms include: 1) conditioning mechanisms; 2) repeated stimulation of a given underlying DA circuit resulting in a lowered threshold for a specific set of prepotent behaviors; 3) electrophysiological reorganization; 4) supersensitive receptor mechanisms; 5) chronic catecholamine depletion and/or enzyme induction resulting in altered neurotransmitter ratios; 6) chronic changes secondary to the route of administration of induction of seizure activity. The proposed research objectives are to further delineate these mechanisms by: 1) analysis of frequency-specific components of motility induced by chronic stimulant intoxication using a special transducer; 2) use of the frequency-dependent measure to determine systemic and cannula-applied neurotransmitter agonist and antagonist contributions to the end-stage behavior; 3) determination of chronic electrophysiological changes by examination of thresholds and propagation of evoked responses, after discharges, and caudate spindles, as well as alterations of synchrony for spontaneous rhythms; 4) use of startle reaction as a model for hyperreactive end-stage behaviors; 5) further examination of route-of-administration effect on tolerance and reverse tolerance.